A patient may have somatic symptoms such as burning pain in arms or feet, numbness in fingers or toes, electric shock-like or pins-and-needles sensations, reduced pin-prick or thermal sensation in the area of arms or feet. These symptoms are usually associated with small fiber neuropathy indicative of many illnesses such as diabetes, connective tissue disease, dysthyroid ophtalmopathy, HIV infection, hepatitis C, neurotoxic drug exposure, Lyme disease, paraneoplastic syndrome, vitamin B12 deficiency, celiac disease, lupus, as well as due to nerve injuries sustained in many professional sports or in military combat. Small fibers are a type of sensory nerve receptors that send signals to the brain and respond with a perception of pain if a potentially damaging thermal stimulus is acting. Thermal stimuli are detected by nerve endings called nociceptors, which are found in the epidermis and on internal surfaces such as the periosteum or joint surfaces. The concentration of nociceptors varies throughout the body, as they are found in greater numbers in the epidermis than in deep internal surfaces. All nociceptors are free nerve endings that have their cell bodies outside the spinal column in the dorsal root ganglia and are named according to their appearance at their sensory. Nociceptors have a certain threshold, that is, they require a minimum intensity of stimulation before they trigger a signal. Once this threshold is reached a signal is passed along the axon of the neuron into the spinal cord. Nociception has been documented in non-mammalian animals, including fishes and a wide range of invertebrates, including leeches, nematode worms, sea slugs, and fruit flies. As in mammals, nociceptive neurons in these species are typically characterized by responding preferentially to high temperature such as 40° Celsius or more, low pH, capsaicin, and tissue damage. The results of our experiments obtained with the technology disclosed in the present invention are a good indicator of what to expect in human subjects because the nerves in earthworms are unmyelinated like the C fibers in humans.
Slow pain is transmitted via slower type C fibers to laminae II and III of the dorsal horns, together known as the substantia gelatinosa. Impulses are then transmitted to nerve fibers that terminate in lamina V, also in the dorsal horn, synapsing with neurons that join fibers from the fast pathway, crossing to the opposite side via the anterior white commissure, and traveling upwards through the anterolateral pathway. These neurons terminate throughout the brain stem, with one tenth of fibres stopping in the thalamus and the rest stopping in the medulla, pons and periaqueductal grey of the midbrain tectum. Fast pain travels via type A-δ fibers to terminate in the dorsal horn of the spinal cord where they synapse on dendrites of the neospinothalamic tract. The axons of these neurons cross the midline (decussate) through the anterior white commissure and ascend contralaterally along the anterolateral columns. These fibers terminate on the ventrobasal complex of the thalamus and synapse with the dendrites of the somatosensory cortex. Fast pain is felt within a tenth of a second of application of the pain stimulus and is sharp and acute in response to thermal stimulation.
In general, a small fiber neuropathy is diagnosed either by biopsy or by elimination, after several other tests are performed to rule out or identify as co-existent other neuropathies. The commonly accepted practice as per recommendations of the U.S. Neurology Board is to diagnose small fiber neuropathies indirectly due to the lack of reliable techniques that can identify these types of neuropathies directly. Electromyograms (EMG) are the standard diagnostic technique for large fiber neuropathies and are used when the patient complains of neurological symptoms that may be due to small fiber, large fiber or a combination of fiber damage. However, preserved functions in small fiber neuropathy are motor strength, tendon reflexes, or proprioception; therefore techniques performed on large fibers do not give information about small fibers. Other diagnostic techniques are nerve conduction tests or quantitative sensory testing, both for large fibers and therefore not relevant to small fiber degeneration. Contact heat evoked potentials record electrical signals that are mostly from A-δ fibers and do not test intra-epidermal C fiber nerves. There is a need for objective investigations of nociceptor fiber loss or dysfunction to diagnose sensory small fiber neuropathy. Our testing technique disclosed in the present invention targets both C and Aδ fibers.
A nerve skin biopsy determines through microscope analysis the density of small fibers in the epidermis. The number of small fibers is counted per given volume of tissue. The technique involves inserting a biopsy needle into the arm or leg of the patient and removing enough tissue to be analyzed by a pathologist under the microscope. A regular neurology practice does not perform skin biopsies, and the patient is sent to a hospital for further diagnostic testing. Our technique disclosed in the present invention is more advantageous than a biopsy because it provides the opportunity of immediate test results with no waiting for results to be analyzed post-procedure and then mailed to the patient.
For the alternate embodiment of the present invention: In many surgical instruments, a high frequency electrical current passes through tissue to create a certain clinical effect. Whether they are for electrocautery, coagulation, or electrosurgery, the instruments have a common characteristic, namely production of heat and heat interaction with tissue. Heating effects produced by the surgical instrument determine the clinical outcome of the treatment of tissue. Coagulation of tissue is the result of protein denaturation due to cumulative heating which means that it is history dependent. As heating power is applied to the area, protein denaturation is determined by the amount of power and the duration of the application. Experience suggests that changes in tissue occur in the first few seconds of exposure to a certain level of heat. After some time, equilibrium is reached and coagulation finally occurs so that an irreversible change of tissue structure takes place. Specifically, below ˜46° C. thermal damage to tissue is reversible. As tissue temperatures exceed 46° C. the proteins in the tissue become permanently denatured losing their structural integrity. Above 90° C. the liquid in the tissue evaporates resulting in significant dehydration.
Radiofrequency generators or ultrasound generators produce currents which induce ionic vibrations. These ionic vibrations cause intracellular heat that results in boiling (explosion) for cutting, or dehydration (dessication) and coagulation. Electrosurgical instruments based on high frequency electrical currents can devitalize tissue at the wound edges leaving dead tissue behind obstructing closure of wounds and predisposing wounds to post-operative infections. However, by slowly heating the tissue at an optimum temperature, a surgical wound can be closed without burning or scarring the surrounding tissue which is what the alternate embodiment of the present invention provides.